Synthetic cannabinoids (also known as synthetic marijuana, noids, herbal incense, K2, or spice) are a class of compounds that bind to cannabinoid receptors to produce cannabis-like subjective effects. Most synthetic cannabinoids are analogs of Δ9-tetrahydrocannabinol (THC), the main active compound of cannabis, while non-psychoactive cannabinoids such as CBD are less well studied. Like THC, most synthetic cannabinoids bind to the same cannabinoid receptors in the brain and are often sold as legal alternatives.
Synthetic cannabinoids are usually sprayed or soaked into dry herbs to look more like marijuana, but pure powder is also available for sale on online research chemical markets. They are commonly smoked or vaporized to achieve a quick onset of effects. They are also orally active when dissolved in a lipid, which can increase the duration significantly. Most are insoluble in water but dissolve in ethanol and lipids.
Unlike cannabis, the chronic abuse of synthetic cannabinoids has been associated with multiple deaths and more dangerous side effects and toxicity in general. Therefore, it is strongly discouraged to take these substances for extended periods of time or in high doses. Additionally, many synthetic cannabinoids have almost little to no human research and some pose more severe health risks than others. It is highly advised to use harm reduction practices if using these substances.
Popular herb blends include K2 and Spice, both of which are generic trademarks used for any synthetic cannabinoid product. Synthetic cannabinoids are often marketed as "herbal incense" and "herbal smoking blends." 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.
Many people have been hospitalized or suffered negative symptoms believing they are comparable to cannabis in potency, harm potential, and effects. This is not the case, and they should be avoided in favour of pure powder.
For a comprehensive list of known synthetic cannabinoid derivatives, /r/Drugs/wiki has published a respectable directory of names and links to further information.
Toxicity and harm potential
Unlike cannabis, there have been multiple deaths associated with the repeated abuse of synthetic cannabinoids as well as serious side effects resulting from its long-term use. 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, agitation, vomiting, hallucinations, psychosis, seizures, and convulsions as well as many others. Sixteen cases of acute kidney injury resulting from synthetic cannabinoid abuse have been reported. JWH-018 has also been associated with strokes in two healthy adults.
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.
These more severe adverse effects in contrast to use of marijuana are believed to stem from the fact that many of the synthetic cannabinoids are full agonists to the cannabinoid receptors, CB1R and CB2R, compared to THC which is only a partial agonist and thus not able to saturate and activate all of the receptor population no matter of dose and resulting concentration.
It is strongly recommended that one use harm reduction practices when using these drugs.
Unlike cannabis, there have been multiple deaths associated with the chronic abuse of synthetic cannabinoid use. Three deaths in Colorado have been investigated for being linked to synthetic cannabis. In addition, five deaths have been associated with the use of 5F-PB-22 in the United States and at least two deaths linked to MDMB-CHMICA. AB-FUBINACA has also been associated with multiple hospitalizations and deaths due to its use.
Like THC, prolonged usage of synthetic cannabinoids may increase one's disposition to mental illness and psychosis, particularly in vulnerable individuals with risk factors for psychotic illnesses (like a past or family history of schizophrenia). It is recommended that individuals with risk factors for psychotic disorders not use synthetic cannabinoids.
In contrast to most other recreational drugs, the dramatic psychotic state induced by the use of synthetic cannabinoids has been reported in multiple cases to persist for several weeks, and in one case for seven months after complete cessation of drug use. It has been suggested that the lack of an antipsychotic chemical (the cannabidiol found in natural cannabis) may make synthetic cannabis more likely to induce psychosis than natural cannabis. As with the acute adverse physical effects, this increase in the risk of psychotic side effects has also been connected to full rather than partial agonism.
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.
When compared to cannabis, the chronic use of synthetic cannabinoids can be considered more moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.
Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The list below includes some known dangerous combinations (although it cannot be guaranteed to include all of them). Independent research (e.g. Google, DuckDuckGo) should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed have been sourced from TripSit.
- Amphetamines - Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences
- Cocaine - Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences
- Roland Macher; Burke, Tod W.; Owen, Stephen S. "Synthetic Marijuana". FBI Law Enforcement Bulletin. | https://leb.fbi.gov/2012/may/synthetic-marijuana
- Mary Carmichael (March 4, 2010). "K2: Scary Drug or Another Drug Scare?". Newsweek | http://www.newsweek.com/k2-scary-drug-or-another-drug-scare-69177
- "What's the buzz?: Synthetic marijuana, K2, Spice, JWH-018 : Terra Sigillata". Scienceblogs.com. | http://scienceblogs.com/terrasig/2010/02/09/k2-spice-jwh018-marijuana/
- 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
- 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/
- 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
- Perspectives of drugs: synthetic cannabinoids in Europe (European Monitoring Centre for Drugs and Drug Addiction | http://www.emcdda.europa.eu/topics/pods/synthetic-cannabinoids
- 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
- Adamowicz P. “Fatal intoxication with synthetic cannabinoid MDMB-CHMICA”. Forensic Sci Int. 2016 Mar;. | https://www.erowid.org/references/refs_view.php?ID=8963
- Synthetic Cannabinoid–Related Illnesses and Deaths | http://www.nejm.org/doi/full/10.1056/NEJMp1505328
- 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
- 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
- Toxicological Findings of Synthetic Cannabinoids in Recreational Users | http://jat.oxfordjournals.org/content/37/8/534.full
- 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
- 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/
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Ischemic stroke after use of the synthetic marijuana "spice". (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/24212384
- Fantegrossi, W. E.; Moran, J. H.; Radominska-Pandya, A; Prather, P. L. (2014). "Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to Δ9-THC: Mechanism underlying greater toxicity?". Life Sciences 97 (1) (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/24084047
- 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
- “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
- 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
- Hurst, D; Loeffler, G; McLay, R (October 2011). "Psychosis associated with synthetic cannabinoid agonists: a case series.". The American Journal of Psychiatry 168 (10) (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/21969050
- Murray, R. M., Quigley, H., Quattrone, D., Englund, A., & Di Forti, M. (2016). Traditional marijuana, high‐potency cannabis and synthetic cannabinoids: increasing risk for psychosis. World Psychiatry, 15(3), 195-204. https://doi.org/10.1002/wps.20341
- Naphthalene - United States Environmental Protection Agency | http://www.epa.gov/ttn/atw/hlthef/naphthal.html
- Toxicity and metabolism of methylnaphthalenes: comparison with naphthalene and 1-nitronaphthalene. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/19464565
- Synthetic cannabinoids in herbal products (United Nations Office on Drugs and Crime) | https://www.unodc.org/documents/scientific/Synthetic_Cannabinoids.pdf
- HAMILTON MORRIS: NAPTHALENE IS SO OVER | http://hamiltonmorris.blogspot.co.uk/2010/06/napthalene-is-so-over.html
- Zimmermann, U.; et al. (2009). "Withdrawal phenomena and dependence syndrome after the consumption of "spice gold"". Deutsches Arzteblatt international 106 (27): 464–467. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719097/