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cannabinoid (spice, K2, AMB-FUBINACA)

Classification: - synthetic cannabioids (spice, K2, black mamba) are produced by spraying psychoactive chemicals onto a plant, which is then smoked or ingested - endocannabinoids Physiology: - humans produce 2 endogenous cannabinoids & 2 receptors for cannabinoids - the cannabinoid system plays a role in: a) food intake & energy balance b) progression of atherosclerosis (CB2 receptor) c) euphoria of runner's high [14] Pharmacology: - endocannabinoid modulator ABX-1431 improves tics in patients with Tourette syndrome [7] - of little or no benefit in multiple sclerosis [9] Indications: - neuropathic pain, - chemotherapy-induced nausea/vomiting - spasticity associated with multiple sclerosis Contraindications: - not for treatment of mental health disorders [11] - does not reduce opioid prescriptions or fatal opioid overdose [22] Benefit/risk: - no convincing evidence on benefits vs risks in older adults [13] - placebo has a significant association with pain reduction in cannabinoid clinical trials [18] - some cannabis products (synthetic products with high THC/CBD ratio) may be associated with short-term improvements in chronic neuropathic pain - dizziness & sedation limit benefit [15] - insufficient evidence for clinical use [16] - extracted products with high THC/CBD ratio (i.e. natural products) associated with dizziness [15,17] - cannabinoids may - lower risk for seizures in various forms of epilepsy [19] - reduce pain & spasticity in multiple sclerosis [19] - improve pain control in palliative care & other conditions [19] - increase risk of psychosis in the general population & especially in adolescents [19] - increase risk for other psychiatric symptoms, including depression & mania [19] - impair recall & learning [19] - increase risk of motor vehicle accidents [19] - increase risks for somnolence, dizziness, & vertigo [19] - increase risk of low-birth weight infants [19] Adverse effects: - acute renal failure associated with synthetic cannabinoids [2] - delirium, agitation, psychosis, confusion most commonly reported with synthetic cannabinoids [3] - tachycardia [3] - hypertension [20] - vomiting [3] - drowsiness/lethargy & coma [3] - 456 patients treated for synthetic cannabinoid intoxication at 50 Toxic sites between 2010-2015* [4] - 3 deaths recorded - synthetic cannabinoids sole toxic exposure in ~60% - coma or CNS depression with synthetic cannabinoids alone vs cannabis alone (29% vs 11%); seizures also more common (19% vs 6%) [10] - AMB-FUBINACA is 85 times as potent as THC & 50 times as potent as K2 - July 12, 2016 incident involving 33 people in New York City, of whom 18 were sent to local hospitals. - described by witness as "like a scene out of a zombie movie" - one patient described as "lethargic but arousable to tactile stimuli"; symptoms resolved in 9 hours [5] - severe bleeding noted in 94 persons March 10-April 5, 2018 after using synthetic cannabinoids spice, K2 - 89 victims in Illinois - contamination of cannabinoid with brodifacoum in at least 18 cases [6] - > 200 people in 9 states with serious, unexplained bleeding linked to synthetic cannabinoids thought to be laced with rat poison - gross hematuria (56%) abdominal pain (47%) most common symptoms [8] - coma, agitation, seizure, acute respiratory failure, QT prolongation, rhabdomyolysis [12] - other drugs may contribute to toxicity [12] * increase in toxicity cases occurred in the Northeast, largely in New York City [4] Laboratory: - cannabinoid in specimen - cannabinoid in hair - cannabinoid in body fluid - cannabinoid in dialysis fluid - cannabinoid in gastric fluid - cannabinoid in meconium - cannabinoid in blood - cannabinoid in serum/plasma - cannabinoid in serum/plasma/blood (screen) - cannabinoid in saliva - cannabinoid in stool - cannabinoid in urine - synthetic cannabinoids do not show in urine drug tests - cannabinoid in vitreous fluid - serum creatine kinase normal [20] - CSF analysis normal [20]

Interactions

drug adverse effects of psychotropic agents

Related

cannabinoid in urine cannabinoid receptor

Specific

cannabidiol (Epidiolex, Zygel, ZYN002, CBD) cannabinol nabilone (Cesamet) tetrahydrocannabinol; delta-9-tetrahydrocannabinol; THC

General

psychotropic agent

References

  1. Journal Watch 25(12):98, 2005 Steffens S, Veillard NR, Arnaud C, Pelli G, Burger F, Staub C, Karsak M, Zimmer A, Frossard JL, Mach F. Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature. 2005 Apr 7;434(7034):782-6. Erratum in: Nature. 2005 May 26;435(7041):528. Karsak, Meliha [added]. PMID: 15815632
  2. Centers for Disease Control and Prevention Acute Kidney Injury Associated with Synthetic Cannabinoid Use - Multiple States, 2012. MMWR. Feb 15, 2013 / 62(06);93-98 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6206a1.htm
  3. Law R et al Notes from the Field: Increase in Reported Adverse Health Effects Related to Synthetic Cannabinoid Use - United States, January-May 2015. MMWR Weekly. June 12, 2015 / 64(22);618-619 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6422a5.htm
  4. Riederer AM, Campleman SL, Carlson RG, et al. Acute Poisonings from Synthetic Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010-2015. MMWR Morb Mortal Wkly Rep 2016;65:692-695 http://www.cdc.gov/mmwr/volumes/65/wr/mm6527a2.htm
  5. Adams AJ, Banister SD, Irizarry L et al "Zombie" Outbreak Caused by the Synthetic Cannabinoid AMB-FUBINACA in New York. N Engl J Med. December 14, 2016 PMID: 27973993 http://www.nejm.org/doi/full/10.1056/NEJMoa1610300
  6. Thayer K. Synthetic pot warning issued as number of users experiencing severe bleeding jumps to 32. Chicago Tribune. March 30, 2018 http://www.chicagotribune.com/news/local/breaking/ct-met-fake-weed-synthetic-cannabis-warning-20180329-story.html - Illinois Department of Public Health. March 30, 2018 Synthetic Cannabinoids http://www.dph.illinois.gov/topics-services/prevention-wellness/medical-cannabis/synthetic-cannabinoids - Brooks M Synthetic Cannabis Laced With Poison Linked to Severe Bleeding, CDC Warns. Medscape. Apr 06, 2018. https://www.medscape.com/viewarticle/894891 - Centers for Disease Control & Prevention (CDC). April 5, 2018 Outbreak Alert: Potential Life-Threatening Vitamin K-Dependent Antagonist Coagulopathy Associated With Synthetic Cannabinoids Use. https://content.govdelivery.com/accounts/USCDC/bulletins/1e6dac3 - Brooks M CDC Warning: Severe Bleeding Linked With Synthetic Cannabinoids. Medscape. May 25, 2018. https://www.medscape.com/viewarticle/897268 - Centers for Disease Control & Prevention (CDC) Outbreak of Life-threatening Coagulopathy Associated with Synthetic Cannabinoids Use. CDC Health Alert Network. May 25, 2018, https://emergency.cdc.gov/han/han00410.asp
  7. Monaco K Novel Endocannabinoid Modulator Improves Tics in Tourette's. In small study, total number, intensity decreased with minimal side effects, although no change for vocal tics. MedPage Today. April 27, 2018 https://www.medpagetoday.com/meetingcoverage/aan/72575 - Muller-Vahl K, et al ABX-1431, A first-in-class endocannabinoid modulator, improves tics in adult patients with Tourette syndrome. American Academy of Neurology (AAN) 2018; Abstract ES Platform 002
  8. Kelkar AH, Smith NA, Martial A, Moole H, Tarantino MD, Roberts JC. An outbreak of synthetic cannabinoid-associated coagulopathy in Illinois. N Engl J Med 2018 Sep 27; 379:1216-1223 PMID: 30280655 - Connors JM. Hemorrhagic highs from synthetic cannabinoids - A new epidemic. N Engl J Med 2018 Sep 27; 379:1275-1277 PMID: 30257159
  9. Torres-Moreno MC, Papaseit E,Torrens M, et al Assessment of Efficacy and Tolerability of Medicinal Cannabinoids in Patients With Multiple SclerosisA Systematic Review and Meta-analysis. JAMA Network Open. 2018;1(6):e183485. PMID: 30646241 Free PMC Article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2706499 - Slaven M, Levine O. Cannabinoids for Symptoms of Multiple Sclerosis. Benefits to Patients Still Unclear. JAMA Network Open. 2018;1(6):e183484 Not indexed in PubMed https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2706491
  10. Anderson SAR, Oprescu AM, Callelo D et al Neuropsychiatric Sequelae in Adolescents With Acute Synthetic Cannabinoid Toxicity. Pediatrics July 2019 PMID: 31285395 https://pediatrics.aappublications.org/content/early/2019/07/04/peds.2018-2690
  11. Black N, Stockings E, Campbell G et al Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis. Lancet Psychiatry. Oct 28, 2019 PMID: 31672337 https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(19)30401-8/fulltext - D'Souza DC Cannabis in psychiatric disorders: the cart before the horse? Lancet Psychiatry. Oct 28, 2019 PMID: 31672338 https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(19)30375-X/fulltext
  12. Kourouni I et al. Critical illness secondary to synthetic cannabinoid ingestion. JAMA Netw Open 2020 Jul 1; 3:e208516. PMID: 32687586 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2768373
  13. Fick DM Evaluating the Safety of Cannabinoid-Based Medicines for Older Adults. JAMA Netw Open. 2021;4(2):e2035952. Feb 2 PMID: 33528548 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2775734
  14. Reynolds F Runner's High New York Times. March 10, 2021 https://www.nytimes.com/2021/03/10/well/move/running-exercise-mental-effects.html - Siebers M, Biedermann SV, Bindila L et al Exercise-induced euphoria and anxiolysis do not depend on endogenous opioids in humans. Psychoneuroendocrinology. 2021 Apr;126:105173 PMID: 33582575 https://www.sciencedirect.com/science/article/abs/pii/S0306453021000470
  15. McDonagh MS et al. Cannabis-based products for chronic pain: A systematic review. Ann Intern Med 2022 Jun 7; [e-pub]. PMID: 35667066 Review. https://www.acpjournals.org/doi/10.7326/M21-4520 - Boehnke KF, Clauw DJ. Cannabinoids for chronic pain: Translating systematic review findings into clinical action. Ann Intern Med 2022 Jun 7; [e-pub] PMID: 35667063 https://www.acpjournals.org/doi/10.7326/M22-1512
  16. Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  17. Sinert RH, Lutsep HL, Khardori R. Rapid Review Quiz: Cannabis. Medscape. August 24, 2022 https://reference.medscape.com/viewarticle/979179
  18. Gedin F, Blome S, Ponten N et al Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain. A Systematic Review and Meta-analysis. JAMA Netw Open. 2022;5(11):e2243848 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799017
  19. Solmi M et al. Balancing risks and benefits of cannabis use: Umbrella review of meta-analyses of randomised controlled trials and observational studies. BMJ 2023 Aug 30; 382:e072348. PMID: 37648266 PMCID: PMC10466434 Free PMC Article https://www.bmj.com/content/382/bmj-2022-072348
  20. NEJM Knowledge+
  21. Frellick M Three Conditions for Which Cannabis Appears to Help MDedge. 2-24. May 3 https://ma1.mdedge.com/internalmedicine/article/268972/neurology/three-conditions-which-cannabis-appears-help
  22. Nguyen HV, McGinty EE, Mital S et al Recreational and Medical Cannabis Legalization and Opioid Prescriptions and Mortality.