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K2 and related Synthetic Cannabinoids. Amber Covey PharmD Candidate. K2 – What is it?. K2 is also commonly called:. Spice Silver Spice Gold Spice Diamond Genie Yucatan Fire Skunk Sence Red Dragon Smoke. The back of a Spice Gold Packet.

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k2 and related synthetic cannabinoids

K2 and related Synthetic Cannabinoids

Amber Covey PharmD Candidate

k2 is also commonly called
K2 is also commonly called:

Spice Silver

Spice Gold

Spice Diamond


Yucatan Fire



Red Dragon Smoke

the back of a spice gold packet
The back of a Spice Gold Packet

The label states “An exotic blend of herbs and extracts. To be used for aromatherapy incense only. Not for human consumption”

what is it
What is it?
  • Been sold in Europe since 2004, possible earlier
    • Because widely used in 2007 and were monitored by the European early warning system on new drugs starting in 2008
  • All these products are commercially sold as incense
  • They are usually marked with a warning that states “not for human consumption”
  • They are a mixture of herbs that are sprayed with synthetic cannabinoids
  • They are currently being abused as a “legal” substitute to marijuana
what s in it
What’s in it?
  • The exact make up of these products varies by name and by batches of the same product
  • Ingredients are not properly labeled on the packaging
  • Some packages are believed to contain heavy metal residues

Vardakou L. TOXLET. 2009; 197:157.

what s in it possible herbs
What’s in it? – Possible Herbs
  • Herbal Components are believed to include:
    • IndianWarrior- Pedicularisdensiflora *
    • Lion’s Tail - Leonotisleonurus *
    • Baybean- Canavaliamaritima
    • Blue Lotus - Nymphaeacaerulea & Nymphaea alba
    • Vanilla
    • Honey, and more
      • *Are both herbs with possible psychoactive effects in and of themselves

Vardakou L. TOXLET. 2009; 197:157.

synthetic cannabinoids
Synthetic Cannabinoids
  • There are potentially 100s of synthetic cannabinoids that can be used but currently the DEA only lists the following as ingredients in spice and considers them drugs of concern
      • HU-211- (dexanabinol, (6aS,10aS)-9-(hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol)
      • JWH-073 - 1-Butyl-3-(1-naphthoyl)indole
      • JWH-018 - 1-Pentyl-3-(1-naphthoyl)indole
      • CP 47,497 - 2-[(1R,3S)-3-hydroxycyclohexyl]-5-(2-methyloctan-2-yl)phenol)
      • HU-210 - is currently classified as a schedule I under the federal Controlled Substance ACT (CSA)
    • Other possible synthetic cannabinoids used in these products include, JWH-398 and JWH-250

DEA. Available from: http://www.deadiversion.usdoj.gov/drugs_concern/spice/index.htm

Vardakou L. TOXLET. 2009; 197:157.

synthetic cannabinoids1
Synthetic Cannabinoids
  • Synthetic Cannabinoids are a structurally diverse class of mostly synthetic substances that bind to cannabinoid receptors
  • The synthetic cannabinoids are exploited because of their similar effects to tetrahydrocannabinol (THC) which is the active ingredient in marijuana
hu 210 and hu 211
HU-210 and HU-211
  • Are some of the first synthetic cannabinoids produced
  • Were developed in the 1960s at Hebrew University
    • Which is where the HU in the title comes from
  • Are structurally similar to THC
  • HU-210 is currently controlled under the federal CSA, though HU-211 is not

DEA. Available from: http://www.deadiversion.usdoj.gov/drugs_concern/spice/spice_hu211.htm.

DEA. Available from: http://www.deadiversion.usdoj.gov/drugs_concern/spice/spice_hu210.htm.

cp 47 497
CP 47, 497
  • Pfizer developed the cyclohexylphenol (CP) series in the 1970s
  • They were developed as a possible pain treatment
  • They are often the first compound to be referred to as a “non-classical” cannabinoid since it’s structurally different from THC
  • CP 47,497 (left) THC (right)

DEA. Available from: http://www.deadiversion.usdoj.gov/drugs_concern/spice/spice_cp47497.htm

jwh 018 and jwh 073
JWH-018 and JWH-073
  • In the 1990s at Clemson University, these compounds were discovered by J.W. Huffman
  • They too are not structurally similar to THC, yet they are cannabinoids receptor agonists
  • They currently are not controlled under the CSA
  • JWH-018 (left) THC (middle) JWH-073 (right)

DEA. Available from: http://deadiversion.usdoj.gov/drugs_concern/spice/spice_jwh018.htm.

DEA. Available from: http://deadiversion.usdoj.gov/drugs_concern/spice/spice_jwh073.html

synthetic cannabinoids2
Synthetic Cannabinoids
  • Hard to identify what Cannabinoids are used in the products due to manufactures changing which synthetic cannabinoid are used as laws try to ban them
  • Also some blends contain a high amount of tocopherol (vitamin E) which aids in masking the cannabinoids from detection
  • Currently after use it does not show up on an urinalysis drug screen

Griffiths P. Addiction. 2010; 105: 951.

signs and symptoms
Signs and Symptoms
  • Present similar to patients who have used marijuana except
    • The following are side effects that are not commonly associated with marijuana use:
      • Increased Heart Rate
      • Increased Blood Pressure
      • Extreme Anxiety
      • Vomiting
      • Tremors
      • Hallucinations
      • Seizures
medical uses
Medical Uses
  • Originally theses synthetic Cannabinoids were developed in research labs as a possible pharmaceutical agents
    • Originally a lot were used to try to develop new drugs for pain management but currently there are no approved medical uses for these compounds
  • All five synthetic cannabinoids display similar pharmacological action to THC by acting on Cannabinoids1/Cannabinoids2 receptor (CB1/CB2) with greater affinity than THC
  • CB1 receptor is located mostly in the Central Nervous System and is associated with psychoactive effects

EMCDDA. 2009. Available from: http://www.emcdda.europa.eu/html.cfm/index90917EN.html

potential for addiction
Potential for Addiction
  • Reported by many users as addictive on internet forums
  • One case report in literature is from Germany and describes a 20 year old male’s treatment to his withdrawal from Spice Gold
    • He presented to the hospital and on day one of admission he had no signs or symptoms
    • On day two he reported internal unrest, and a very intense craving for the drug
    • Author concluded that the patient’s presentation was consistent with the diagnoses of withdrawal.

Zimmerman US. Deutsches Aerzteblatt Intern. 2009; 106:464.

auw rter et al self experiment
Auwärter et al. Self-Experiment
  • In 2008, a study was released titled “‘Spice’ and other herbal blends: harmless incense or cannabinoid designer drugs?” in the Journal of Mass Spectrometry
  • It was a self-experiment on the effects of Spice by two of the authors to prove the pharmacological activity and gain positive drug samples of blood and urine
    • They smoked 0.3g of Spice Diamond
    • Then several blood and urine samples were taken

Auwarter V. J. Mass Spectrom. 2009; 44:832.

auw rter et al self experiment results
Auwärter et al. Self-Experiment - Results
  • It was noted that:
    • “Approximately 10 min post-application the first noticeable effects occurred in the form of considerable reddened conjunctivae, significant increase of pulse rates, xerostomia and an alteration of mood and perception.”
    • While the authors felt impaired, none of the psychomotor tests performed were abnormal
    • Screening with a common immunoassay for the major metabolite of THC was negative for all the blood and urine samples

Auwarter V. J. Mass Spectrom. 2009; 44:832.

spice and the military
Spice and the Military
  • The Marine Forces Pacific issued a punitive order on December 1, 2009 banning the use and possession of Spice
  • Due to an increasing trend of abuse among the military its use is now banned by the United States Army, United States Air Force, and United States Navy.

Lisbon B. 2009. Available from: http://www.marines.mil/unit/mcasyuma/Pages/20091210Spice.aspx

Vardakou L. TOXLET. 2009; 197:157.

Air Force Guidance Memo to AFI 44-121 . 2010. Available from: http://www.af.mil/shared/media/epubs/AFI44-121.pdf

current legislation
Current Legislation:
  • Many European countries and Canada have placed controls or completely banned the selling of products containing HU-210 and JWH-018
  • March 2010 Kansas became the first state in the United States to take action against the sale of K2 by adding JWH-018, JWH-073, and HU-210 to the list of schedule I drugs

Vardakou L. TOXLET. 2009; 197:157.

Housebill No. 2411. 2010. Available from: http://www.kslegislature.org/bills/2010/2411.pdf

current legislation continued
Current Legislation - continued
  • Many more states and cities have started to propose or have passed bans on synthetic cannabinoids
    • Alabama – banned HU-210, JWH-018, JWH-073
    • Arkansas – banned selling JWH-018, JWH-073 but did not ban possession
    • Georgia – banned JWH-018
    • Iowa – July 21, 2010 passed emergency legislation banning JWH-018, JWH-073, HU-211, and CP 47,497
current legislation continued1
Current Legislation - continued
  • Kentucky – banned synthetic cannabinoid agonist that do not have an approved medical use
  • Louisiana – on June 18, 2010 passed a ban on JWH-018, JWH-073, and CP 47,497 but has an enaction date of December 21, 2012
  • Missouri – outlawed synthetic compounds that mimic marijuana but has an enaction date of August 28, 2010
  • Tennessee – banned JWH-018
  • K2 or Spice is a mix of herbs sprayed with synthetic cannabinoids currently being sold as incense and abused for their marijuana like effects
  • There currently are NO safe and accepted medical uses in the United States and there have been case reports of high abuse risk
  • Many states are currently taking action against this growing phenomenon by adding these synthetic cannabinoids to their controlled substances lists