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Cannabinoid

A flowering cannabis plant, the most common source of cannabinoids.
A bag of Spice brand herbal incense. This contains synthetic cannabinoids which produce a similar effect to that of cannabis.

A cannabinoid is one of a class of diverse chemical compounds that act on cannabinoid receptors on cells that alter neurotransmitter functioning in the brain. These receptor proteins include the endocannabinoids (produced naturally in the body by humans and animals),[1] the phytocannabinoids (found in cannabis and some other plants), and synthetic cannabinoids (manufactured chemically).

The most notable cannabinoid is the phytocannabinoid ∆9-tetrahydrocannabinol (THC), the primary psychoactive compound of cannabis.[2][3] Cannabidiol (CBD) is another major constituent of the plant, representing up to 40% in extracts of the plant resin.[4] There are at least 85 different cannabinoids isolated from cannabis which exhibit varied effects.[5]

Synthetic cannabinoids encompass a variety of distinct chemical classes: the classical cannabinoids structurally related to THC; the nonclassical cannabinoids (cannabimimetics) including the aminoalkylindoles, 1,5-diarylpyrazoles, quinolines, and arylsulphonamides; and eicosanoids related to the endocannabinoids.[6][7]

Contents

Cannabinoid receptors

Before the 1980s, it was often speculated that cannabinoids produced their physiological and behavioral effects via nonspecific interactions instead of interacting with specific receptors directly. 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. At present, there are two known types of cannabinoid receptors, termed CB1 and CB2,[8] with mounting evidence of more.[9][10] However, the role of these interactions and how they result in the cannabinoid high experience continues to remain elusive.

Cannabinoid receptor type 1

CB1 receptors are found primarily in the brain, more specifically in the basal ganglia and in the limbic system (including the hippocampus).[11] They are also found in the cerebellum and in both male and female reproductive systems. CB1 receptors are absent in the medulla oblongata, the part of the brain stem responsible for respiratory and cardiovascular functions. Thus, there is not the risk of respiratory or cardiovascular failure that can be produced by some drugs. CB1 receptors appear to be responsible for the euphoric and anticonvulsive effects of cannabis. However, the role of these interactions and how they result in the cannabinoid high experience continues to remain elusive.

Cannabinoid receptor type 2

CB2 receptors are predominantly found in the immune system, or immune-derived cells[12] with the greatest density in the spleen. While found only in the peripheral nervous system, a report does indicate that CB2 is expressed by a subpopulation of microglia in the human cerebellum.[13] CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis.[14] However, the role of these interactions and how they result in the cannabinoid high experience continues to remain elusive.

Subjective effects

Disclaimer: The effects listed below are cited from the Subjective Effect Index (SEI), which relies on assorted anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be taken with a healthy amount of skepticism. It is worth noting that these effects will not necessarily occur in a consistent or reliable manner, although higher doses (common+) are more likely to induce the full spectrum of reported effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects
 

    • Sedation - Although certain strains of cannabinoids present mild encouraged stimulation at low to moderate doses, for the most part the effects on the user's energy levels are primarily sedating. This encourages one to relax, but can, however, be suppressed by simply forcing oneself to engage in physical activities.
    • Motor control loss - These substances cause a partial to moderate suppression of motor control which intensifies proportional to dosage but rarely results in a complete inability to walk and perform basic movements.
    • Appetite enhancement - The feeling of increased appetite following the use of cannabinoids has been documented for hundreds of years[15] and is known colloquially as "the munchies" in popular American and United Kingdom culture. Clinical studies and survey data have found that cannabis increases food enjoyment and interest in food.[16] This is thought to be due to the way in which endocannabinoids in the hypothalamus activate cannabinoid receptors that are responsible for maintaining food intake.[17]
    • Nausea suppression - Cannabis is effective for suppressing nausea induced by both general illness and substances. It is considered an effective treatment for chemotherapy-induced nausea and vomiting (CINV)[18] and is a reasonable option in those who do not improve following preferential treatment.[19]
    • Dehydration
    • Vasodilation - THC decreases blood pressure which dilates the blood vessels and increases blood flow throughout the body. The arteries in the eyeball expand from the decreased blood pressure. Studies in the 1970s showed marijuana, when smoked or eaten, effectively lowers intraocular pressure by about 25%, as much as standard medications.[20] These enlarged arteries often produce a bloodshot red eye effect. It is precisely this effect on the human eye that makes cannabinoids an effective medicine for glaucoma.[21]
    • Pain relief - This substance has been reported as being useful for treating certain headaches and chronic pain, including pain caused by neuropathy and possibly fibromyalgia and rheumatoid arthritis.[22][23]
    • Perception of increased weight or Perception of decreased weight - Depending on the specific cannabinoid, one can find themselves with a body which can feel either physically heavier or lighter than it usually would in a manner that is entirely dependent upon dosage.
    • Changes in gravity - At extremely high doses, many users report a feeling of being pulled backwards across vast distances at powerful speeds. This sensation progressively increases in intensity and eventually becomes unbearable if one leans backwards or lies down but usually disappears altogether once the user sits up or leans forward.
    • Spontaneous tactile sensations

Visual effects
 

    • Brightness alteration
    • Colour enhancement
    • Visual acuity suppression
    • Geometry - Certain cannabinoids are capable of inconsistently inducing mild to intense psychedelic geometry at high doses. Within many users who also regularly use psychedelics, however, they are capable of inducing these consistently in a visual style which seems to be an averaged out depiction of all the psychedelics one has used within the past. These rarely extend beyond level 4 and are considered to be mild, fine, small and zoomed out (but often well-defined).
    • Internal hallucinations

Cognitive effects
 

Auditory effects
 


Phytocannabinoids

 
Comparison of phytocannabinoids

Phytocannabinoids can be defined as any plant-derived natural product capable of either directly interacting with cannabinoid receptors or sharing chemical similarity with cannabinoids or both. The entourage effect is a proposed mechanism by which compounds present in cannabis which are largely non-psychoactive by themselves modulate the overall psychoactive effects of the plant (these resulting principally from the action of the main psychoactive component of cannabis, tetrahydrocannabinol (THC)).

  • THC
  • CBD
  • CBN
  • CBG (Cannabigerol)
  • CBC (Cannabichromene)
  • CBL (Cannabicyclol)
  • CBV (Cannabivarin)
  • THCV (Tetrahydrocannabivarin)
  • CBDV (Cannabidivarin)
  • CBCV (Cannabichromevarin)
  • CBGV (Cannabigerovarin)
  • CBGM (Cannabigerol Monomethyl Ether)

Plant sources

Synthetic cannabinoids

Main article: Synthetic cannabinoid

Synthetic cannabinoids are any artificial compound which is functionally similar to Δ9-tetrahydrocannabinol (THC), the active principle of cannabis. Like THC, they bind to the same cannabinoid receptors in the brain and are often sold as legal alternatives.

Toxicity and harm potential

Main article: Synthetic cannabinoid § Toxicity and harm potential

Unlike cannabis, there have been multiple deaths[24][25][26][27][28][29][30] associated with the repeated abuse of synthetic cannabinoids as well as serious side effects resulting from its long-term use.[31][32][33] Therefore, it is strongly discouraged to take this substance for extended periods of time or in excessive doses. Compared to cannabis and its active cannabinoid THC, the adverse effects are often much more severe and can include high blood pressure, increased heart rate, heart attacks,[34][35] agitation,[36] vomiting,[37][38][39] hallucinations,[40] psychosis,[41][42][36][43] seizures,[44][45][46] and convulsions[47][48] as well as many others. Sixteen cases of acute kidney injury resulting from synthetic cannabinoid abuse have been reported.[49] JWH-018 has also been associated with strokes in two healthy adults.[50]

It should be noted that pre-mixed, branded blends (like Spice and K2) are more dangerous than pure powder because the specific chemicals and dosages are usually unlisted as well as the potential of inconsistent areas of dense powder, leading to an overdose. As synthetic cannabinoids are active in the milligram range (with below 5mg being a common dose), it is important to use proper precautions when dosing to avoid a negative experience.

Like THC, prolonged usage of synthetic cannabinoids may increase one's disposition to mental illness and psychosis[42], particularly in vulnerable individuals with risk factors for psychotic illnesses (like a past or family history of schizophrenia).[51][52][36] It is recommended that individuals with risk factors for psychotic disorders not use synthetic cannabinoids.[53]

Although there is no valid data on the toxicity of synthetic cannabinoids so far, there is concern that the naphthalene group found in THJ-018 and some other synthetic cannabinoids may be toxic or carcinogenic.[54][55][56][57]

It is strongly recommended that one use harm reduction practices when using these drugs.

Common substances

Brand-name mystery blends

 
Comparison of synthetic cannabinoids

Please be aware that pre-mixed, branded blends are unreliable as they often fail to list the constituents and dosages. Many people have been hospitalised or suffered negative symptoms believing they are comparable to cannabis in potency and effects. This is not the case, and they should be avoided in favour of pure analytical samples where possible.

Indazolecarboxamides

Indolecarboxamides

Indolecarboxylates

Naphthoylindoles

Naphthoylindazoles

Tetramethylcyclopropanoylindoles

Comprehensive List

For a comprehensive list of known synthetic cannabinoid derivatives, /r/Drugs/wiki has published a respectable directory of names and links to further information.

External links

References

  1. ↑ The endocannabinoid system as an emerging target of pharmacotherapy (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16968947
  2. ↑ The endocannabinoid system: drug targets, lead compounds, and potential therapeutic applications (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16078824
  3. ↑ Pertwee, Roger, ed. (2005). Cannabinoids. Springer-Verlag. p. 2. ISBN 3-540-22565-X.
  4. ↑ http://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1962-01-01_3_page005.html
  5. ↑ http://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1962-01-01_3_page005.html
  6. ↑ The endocannabinoid system: drug targets, lead compounds, and potential therapeutic applications (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16078824
  7. ↑ Pertwee, Roger, ed. (2005). Cannabinoids. Springer-Verlag. p. 2. ISBN 3-540-22565-X.
  8. ↑ The endocannabinoid system as an emerging target of pharmacotherapy (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16968947
  9. ↑ Evidence for novel cannabinoid receptors | The human brain has more cannabinoid receptors than any other G protein-coupled receptor (GPCR) type.
  10. ↑ Boron, Walter F.; Boulpaep, Emile L., eds. (2009). Medical Physiology: A Cellular and Molecular Approach. Saunders. p. 331. ISBN 978-1-4160-3115-4.
  11. ↑ The endocannabinoid system as an emerging target of pharmacotherapy (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16968947
  12. ↑ Is lipid signaling through cannabinoid 2 receptors part of a protective system? (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/21295074
  13. ↑ Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an immunohistochemical study (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/15266552
  14. ↑ Is lipid signaling through cannabinoid 2 receptors part of a protective system? (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/21295074
  15. ↑ Mechoulam, R. (1984). Cannabinoids as therapeutic agents. Boca Raton, FL: CRC Press. ISBN 0-8493-5772-1.
  16. ↑ How Marijuana Works | http://science.howstuffworks.com/marijuana4.htm
  17. ↑ How Marijuana Works | http://science.howstuffworks.com/marijuana4.htm
  18. ↑ The Pharmacologic and Clinical Effects of Medical Cannabis | http://onlinelibrary.wiley.com/doi/10.1002/phar.1187/abstract;jsessionid=1E004D7B7E2B5CA792E75A6E83EEC59C.f03t01
  19. ↑ The Therapeutic Potential of Cannabis and Cannabinoids | http://www.aerzteblatt.de/int/archive/article?id=127603
  20. ↑ Cardiovascular Effects of Cannabis | http://www.idmu.co.uk/canncardio.htm
  21. ↑ Is Marijuana an Effective Treatment for Glaucoma? | http://medicalmarijuana.procon.org/view.answers.php?questionID=000140
  22. ↑ Systematic Review and Meta-analysis of cannabinoids Treatment for Chronic Pain | http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4637.2009.00703.x/abstract
  23. ↑ Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials | http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2011.03970.x/abstract
  24. ↑ Brents, L. K.; Reichard, E. E.; Zimmerman, S. M.; Moran, J. H.; Fantegrossi, W. E.; Prather, P. L. (2011). "Phase I hydroxylated metabolites of the K2 synthetic cannabinoid JWH-018 retain in vitro and in vivo cannabinoid 1 receptor affinity and activity". PLoS ONE 6 (7) (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/21755008
  25. ↑ Coroner: Lamar Jack ingested chemical found in fake marijuana before he died (IndependentMail.com) | https://web.archive.org/web/20131009101212/http://www.independentmail.com/news/2011/oct/15/coroner-lamar-jack-ingested-chemical-found-fake-ma/
  26. ↑ Coffman, K. (6 September 2013). "Colorado probes three deaths possibly linked to synthetic marijuana". Reuters (Denver). | http://www.reuters.com/article/us-usa-colorado-spice-idUSBRE98516A20130906
  27. ↑ Perspectives of drugs: synthetic cannabinoids in Europe (European Monitoring Centre for Drugs and Drug Addiction | http://www.emcdda.europa.eu/topics/pods/synthetic-cannabinoids
  28. ↑ Westin AA, Frost J, Brede WR, Gundersen PO, Einvik S, Aarset H, Slørdal L. “Sudden Cardiac Death Following Use of the Synthetic Cannabinoid MDMB-CHMICA”. J Anal Toxicol. 2016 Jan 19;40(1):86-7. | https://www.erowid.org/references/refs_view.php?ID=8961
  29. ↑ Adamowicz P. “Fatal intoxication with synthetic cannabinoid MDMB-CHMICA”. Forensic Sci Int. 2016 Mar;. | https://www.erowid.org/references/refs_view.php?ID=8963
  30. ↑ Synthetic Cannabinoid–Related Illnesses and Deaths | http://www.nejm.org/doi/full/10.1056/NEJMp1505328
  31. ↑ Vardakou, I; Pistos, C; Spiliopoulou, Ch (2010). "Spice drugs as a new trend: Mode of action, identification and legislation". Toxicology Letters 197 (3): 157–62. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/20566335
  32. ↑ Auwärter, V.; et al. (2009). "'Spice' and other herbal blends: harmless incense or cannabinoid designer drugs?". Journal of mass spectrometry : JMS 44 (5) | http://onlinelibrary.wiley.com/doi/10.1002/jms.1558/abstract
  33. ↑ Toxicological Findings of Synthetic Cannabinoids in Recreational Users | http://jat.oxfordjournals.org/content/37/8/534.full
  34. ↑ Mir, A; Obafemi, A; Young, A; Kane, C (December 2011). "Myocardial infarction associated with use of the synthetic cannabinoid k2.". Pediatrics 128 (6) | http://pediatrics.aappublications.org/content/pediatrics/early/2011/11/04/peds.2010-3823.full.pdf
  35. ↑ Acute myocardial infarction, associated with the use of a synthetic adamantyl-cannabinoid: a case report (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715335/
  36. ↑ 36.0 36.1 36.2 A Teenager With Agitation: Higher Than She Should Have Climbed - Pediatric Emergency Care: June 2010 - Volume 26 - Issue 6 - pp 462-465 | http://journals.lww.com/pec-online/Abstract/2010/06000/A_Teenager_With_Agitation__Higher_Than_She_Should.16.aspx
  37. ↑ T. "Extreme Nausea, Incoherent: An Experience with JWH-018 (ID 84443)". Erowid.org. Oct 12, 2010. erowid.org/exp/84443 | https://www.erowid.org/experiences/exp.php?ID=84443
  38. ↑ Exdrugaddict. "Playing With Fire: An Experience with Spice (ID 90178)". Erowid.org. Dec 16, 2013. erowid.org/exp/90178 | https://www.erowid.org/experiences/exp.php?ID=90178
  39. ↑ Boss Lok. "Non-Allergic Adverse Reaction: An Experience with Spice and Synthetic Cannabinoids ('Drill') (ID 85853)". Erowid.org. Oct 12, 2010. erowid.org/exp/85853 | https://www.erowid.org/experiences/exp.php?ID=85853
  40. ↑ Jeanna Bryner (March 3, 2010). "Fake Weed, Real Drug: K2 Causing hallucinations in Teens". LiveScience. | http://www.livescience.com/6149-fake-weed-real-drug-k2-causing-hallucinations-teens.html
  41. ↑ Every-Palmer, S (2010). "Warning: Legal synthetic cannabinoid-receptor agonists such as JWH-018 may precipitate psychosis in vulnerable individuals". Addiction 105 (10): 1859–60. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/20840203
  42. ↑ 42.0 42.1 Causal association between cannabis and psychosis: examination of the evidence - The British Journal of Psychiatry Jan 2004, 184 (2) 110-117 | http://bjp.rcpsych.org/content/184/2/110.short
  43. ↑ Müller, H.; Sperling, W.; Köhrmann, M.; Huttner, H.; Kornhuber, J.; Maler, J. (2010). "The synthetic cannabinoid Spice as a trigger for an acute exacerbation of cannabis induced recurrent psychotic episodes". Schizophrenia Research 118 (1–3) (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/20056392
  44. ↑ Thisisntover. "Most Insane Hour of My Life: experience with JWH-018 (ID 85936)". Erowid.org. Oct 1, 2010. erowid.org/exp/85936 | http://www.erowid.org/experiences/exp.php?ID=85936
  45. ↑ Michael C. "The Night My Brain Caved: experience with AM-2201 (ID 92954)". Erowid.org. Sep 18, 2012. erowid.org/exp/92954 | https://www.erowid.org/experiences/exp.php?ID=92954
  46. ↑ Steve. "Next-Night Seizures: experience with Products - Spice and Synthetic Cannabinoids ('Apocalypse'?) (ID 89290)". Erowid.org. Feb 3, 2011. erowid.org/exp/89290 | https://www.erowid.org/experiences/exp.php?ID=89290
  47. ↑ ilovethagreenery. "Should've Called Poison Control Bro: An Experience with Products - Spice and Synthetic Cannabinoids ('Diamond Dove') & Alcohol (ID 92698)". Erowid.org. Jan 6, 2012. erowid.org/exp/92698 | https://www.erowid.org/experiences/exp.php?ID=88807 | https://www.erowid.org/experiences/exp.php?ID=88807
  48. ↑ Schneir, AB; Baumbacher, T (December 13, 2011). "Convulsions Associated with the Use of a Synthetic Cannabinoid Product.". Journal of Medical Toxicology 8 (1): 62–4 (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/22160733
  49. ↑ Acute Kidney Injury Associated with Synthetic Cannabinoid Use — Multiple States, 2012 (Centers for Disease Control and Prevention) | http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6206a1.htm
  50. ↑ Ischemic stroke after use of the synthetic marijuana "spice". (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/24212384
  51. ↑ Every-Palmer, S. Synthetic cannabinoid use and psychosis: an explorative study. Journal of Drug and Alcohol Dependence 2011. | https://www.researchgate.net/publication/49831304_Every-Palmer_S_Synthetic_cannabinoid_JWH-018_and_psychosis_An_explorative_study
  52. ↑ “Spice” Girls: Synthetic Cannabinoid Intoxication - The Journal of Emergency Medicine Volume 40, Issue 3, March 2011, Pages 296–299 (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0736467910008802
  53. ↑ Every-Palmer, S (September 1, 2011). "Synthetic cannabinoid JWH-018 and psychosis: an explorative study.". Drug and Alcohol Dependence 117 (2-3): 152–7 (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/21316162
  54. ↑ Naphthalene - United States Environmental Protection Agency | http://www.epa.gov/ttn/atw/hlthef/naphthal.html
  55. ↑ Toxicity and metabolism of methylnaphthalenes: comparison with naphthalene and 1-nitronaphthalene. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/19464565
  56. ↑ Synthetic cannabinoids in herbal products (United Nations Office on Drugs and Crime) | https://www.unodc.org/documents/scientific/Synthetic_Cannabinoids.pdf
  57. ↑ HAMILTON MORRIS: NAPTHALENE IS SO OVER | http://hamiltonmorris.blogspot.co.uk/2010/06/napthalene-is-so-over.html
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