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Recently, there has been an increase in the consumption of designer drugs, substances aimed at producing psychoactive, energizing, euphoric or anesthetic effects. Designer drugs are substitutes of actual narcotics, whose possession is banned under Polish law according to the Act of 29 July 2005. The latest reports suggest that the number of synthetic psychoactive substances is increasing. In the span of 2012, a total of 28 new synthetic cannabinoids were discovered in member states of the European Union. Synthetic psychoactive substances appear in different forms on the market: tablets (often very colourful and interestingly-shaped), seeds, dried product (sprayed with synthetic substance and redried), crystals or powder. The way of application is greatly diverse, and depends on the form in which a drug is produced and dispensed. The methods of intoxication include smoke inhalation (oftentimes blends are smoked), intranasal or oral application, placing crystals on the eye, or injection. Said methods correspond, with varying degrees, to invoking different psychotic effects, such as agitation, panic attacks, paranoia, hallucinations, overall irritation, and aggression. Various cardiovascular effects, such as tachycardia or increase in blood pressure, may follow as well. However, the primary influence is on the nervous system, inhibiting the reuptake of neurotransmitters such as serotonin, noradrenalin and dopamine, and leading to their increased concentration at the presynaptic cleft, which in turn causes feelings of agitation and pleasure. The knowledge regarding the strength, toxicity, and metabolism of designer drugs is yet sparse. The same pertains to the knowledge regarding the handling of overdose cases., (© 2016 MEDPRESS.)

Synthetic indole-derived cannabinoids have become commonly used recreational drugs and continue to be abused despite their adverse consequences. As compounds that were identified early in the epidemic (e.g., naphthoylindoles) have become legally banned, new compounds have appeared on the drug market. Two tetramethylcyclopropyl ketone indoles, UR-144 [(1-pentyl-1H-indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone] and XLR-11 [(1-(5-fluoropentyl)-1H-indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone], recently have been identified in confiscated products. These compounds are structurally related to a series of CB2-selective compounds explored by Abbott Labs. The purpose of the present study was to evaluate the extent to which UR-144 and XLR-11 shared cannabinoid effects with Δ9-tetrahydrocannabinol (Δ9-THC). Indices of in vitro and in vivo activity at cannabinoid receptors were assessed. Similar to other psychoactive cannabinoid agonists, XLR-11 and UR-144 showed low nanomolar (<30) affinity for CB1 and CB2 receptors, activated these receptors as full agonists, and produced dose-dependent effects that were blocked by rimonabant in mice, including antinociception, hypothermia, catalepsy and suppression of locomotor activity. The potency of both compounds was several-fold greater than Δ9-THC. XLR-11 and UR-144 also substituted for Δ9-THC in a Δ9-THC discrimination procedure in mice, effects that were attenuated by rimonabant. Analysis of urine from mice treated with the compounds revealed that both were extensively metabolized, with predominant urinary excretion as glucuronide conjugates. Together, these results demonstrate that UR-144 and XLR-11 share a pharmacological profile of in vitro and in vivo effects with Δ9-THC and other abused indole-derived cannabinoids and would be predicted to produce Δ9-THC-like subjective effects in humans., (Copyright © 2013 Elsevier Ltd. All rights reserved.)