Psychiatric Sequelae of Spice, K2, and Synthetic Cannabinoid Receptor Agonists

Benford, Dawn M.; Caplan, Jason P.

doi:10.1016/j.psym.2011.01.004

Cited by 59 publications

(53 citation statements)

References 3 publications

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“…It was reported that severe and persistent psychotic symptoms might be developed after SC use in some cases (24). Therefore, sometimes it may be very difficult to differentiate psychiatric pictures evolved after SC use from primary psychiatric diseases (25).…”

Section: Discussionmentioning

confidence: 99%

Capgras syndrome after use of synthetic cannabinoids: an adolescent case

Özer¹,

Çeri²,

Evren³

2016

Dusunen Adam

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Section: Discussionmentioning

confidence: 99%

Capgras syndrome after use of synthetic cannabinoids: an adolescent case

Özer¹,

Çeri²,

Evren³

2016

Dusunen Adam

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“…Whereas use of cannabis, which contains the natural psychoactive cannabinoid ⌬ 9 -tetrahydrocannabinol (⌬ 9 -THC), is often associated with mild symptoms such as appetite stimulation and orthostatic hypotension (Jones, 2002;Randall et al, 2004), K2 users present to emergency departments with severe adverse effects including hypertension, visual and auditory hallucinations, tachycardia, sinus bradycardia, chest pain, dysrhythmias, seizures, psychosis, intracranial hemorrhage, and even death (Mü ller et al, 2010;Vearrier and Osterhoudt, 2010;Benford and Caplan, 2011;Every-Palmer, 2011;Lapoint et al, 2011;Schneir et al, 2011;Simmons et al, 2011a,b;Young et al, 2011;Pant et al, 2012). In addition, recent medical reports indicate that chronic K2 use may lead to the development of tolerance, dependence, and withdrawal (Zimmermann et al, 2009), as has been observed with marijuana abuse (Budney and Hughes, 2006).…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450-Mediated Oxidative Metabolism of Abused Synthetic Cannabinoids Found in K2/Spice: Identification of Novel Cannabinoid Receptor Ligands

et al. 2012

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Abuse of synthetic cannabinoids (SCs), such as [1-naphthalenyl-(1-pentyl-1H-indol-3-yl]-methanone (JWH-018) and [1-(5-fluoropentyl)-1H-indol-3-yl]-1-naphthalenyl-methanone (AM2201), is increasing at an alarming rate. Although very little is known about the metabolism and toxicology of these popular designer drugs, mass spectrometric analysis of human urine specimens after JWH-018 and AM2201 exposure identified monohydroxylated and carboxylated derivatives as major metabolites. The present study extends these initial findings by testing the hypothesis that JWH-018 and its fluorinated counterpart AM2201 are subject to cytochrome P450 (P450)-mediated oxidation, forming potent hydroxylated metabolites that retain significant affinity and activity at the cannabinoid 1 (CB 1 ) receptor. Kinetic analysis using human liver microsomes and recombinant human protein identified CYP2C9 and CYP1A2 as major P450s involved in the oxidation of the JWH-

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“…The frequent use of CB 1 receptor agonists may lead to pharmacological tolerance and dependence, especially in view of the long-lasting effects of commonly used drugs such as D 9 -THC in marijuana and Marinol or, more recently, synthetic cannabinoids such as JWH-018 or JWH-073 in K2 and Spice (Panagis et al, 2008;Atwood et al, 2011;Benford and Caplan, 2011). However, tolerance does not appear to develop uniformly across studies or ligands.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Tolerance and Behavioral/Physical Dependence during Chronic CB₁Agonist Treatment: Effects of CB₁Agonists, Antagonists, and Noncannabinoid Drugs

Desai

Thakur

Vemuri

et al. 2012

J Pharmacol Exp Ther

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Behavioral studies of chronic CB 1 receptor activation may provide a pharmacological approach to understanding efficacy-related differences among CB 1 ligands as well as mechanistic commonalities between cannabinoid and noncannabinoid drugs. In the present studies, the effects of CB 1 agonists [(6aR,10aR)-3-(1-adamantyl)-6,6,9-trimethyl-6a,7,10,10a-, and dopamine (DA)-related [methamphetamine, (6)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF82958), (R)-(1)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390), (6aR)-5,6,6a,7-tetrahydro-6-propyl-4H-dibenzo[de,g]quinoline-10,11-diol (R-(2)-NPA), haloperidol] and opioid (morphine, naltrexone) drugs on scheduled-controlled responding under a 30-response fixed ratio schedule of stimulus-shock termination in squirrel monkeys were compared before and during chronic treatment with the long-acting CB 1 agonist AM411 (1.0 mg/kg per day, i.m.). Prechronic treatment with all drugs except naltrexone (1-10 mg/kg) produced dose-related decreases in responses rates. Dose-response re-determinations during chronic treatment revealed the following: 1) .250-fold (AM411, methanandamide) and .45-fold (AM4054, WIN55,212.2, D 9 -THC) rightward shifts in the ED 50 values for CB 1 agonists; 2) .100-fold and .20-fold leftward shifts in the ED 50 values for SR141716A and AM4113, respectively; and 3) approximately 4.8-fold and 10-fold rightward shifts in the ED 50 values for methamphetamine and the DA D 2 agonist R-(2)-NPA, respectively. Dose-response relationships for other DA-related and opioid drugs were unchanged by chronic CB 1 agonist treatment. Differences in the magnitude of tolerance among CB 1 agonists during chronic treatment may be indicative of differences in their pharmacological efficacy, whereas the enhanced sensitivity to behaviorally disruptive effects of CB 1 antagonists may provide evidence for CB 1 -related behavioral and/or physical dependence. Finally, the development of crosstolerance to methamphetamine and R-(2)-NPA bolsters previous evidence of interplay between CB 1 and DA D 2 signaling mechanisms.

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Psychiatric Sequelae of Spice, K2, and Synthetic Cannabinoid Receptor Agonists

Cited by 59 publications

References 3 publications

Capgras syndrome after use of synthetic cannabinoids: an adolescent case

Capgras syndrome after use of synthetic cannabinoids: an adolescent case

Cytochrome P450-Mediated Oxidative Metabolism of Abused Synthetic Cannabinoids Found in K2/Spice: Identification of Novel Cannabinoid Receptor Ligands

Analysis of Tolerance and Behavioral/Physical Dependence during Chronic CB₁Agonist Treatment: Effects of CB₁Agonists, Antagonists, and Noncannabinoid Drugs

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Psychiatric Sequelae of Spice, K2, and Synthetic Cannabinoid Receptor Agonists

Cited by 59 publications

References 3 publications

Capgras syndrome after use of synthetic cannabinoids: an adolescent case

Capgras syndrome after use of synthetic cannabinoids: an adolescent case

Cytochrome P450-Mediated Oxidative Metabolism of Abused Synthetic Cannabinoids Found in K2/Spice: Identification of Novel Cannabinoid Receptor Ligands

Analysis of Tolerance and Behavioral/Physical Dependence during Chronic CB1Agonist Treatment: Effects of CB1Agonists, Antagonists, and Noncannabinoid Drugs

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Analysis of Tolerance and Behavioral/Physical Dependence during Chronic CB₁Agonist Treatment: Effects of CB₁Agonists, Antagonists, and Noncannabinoid Drugs