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Δ9-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids found on the gray market.

Michael B. Gatch, Michael J Forster

Behavioural Pharmacology August 2015 DOI: 10.1097/fbp.0000000000000150 (opens in new tab)

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Characteristics Preclinical behavioral pharmacology experiments Peer reviewed
Population Male Swiss-Webster mice and male Sprague-Dawley rats
Interventions UR-144 XLR-11 AKB-48 (APINACA) PB-22 (QUPIC) 5F-PB-22 AB-FUBINACA Δ-THC
Dose Δ-THC 3 mg/kg, intraperitoneally
Topics Cannabis
Key findings Each of the six synthetic cannabinoids fully substituted for the discriminative stimulus effects of Δ-THC in rats, and all produced locomotor depressant effects in mice, with PB-22 and 5F-PB-22 lasting longer (120-150 minutes) than the others (up to 90 minutes). The authors conclude these findings confirm the suggestion that the compounds have marijuana-like psychoactive effects and abuse liability.

Abstract

When synthetic cannabinoid compounds became controlled by state and federal governments, different, noncontrolled compounds began to appear as marijuana substitutes. Unlike the scheduled cannabinoids, the newer compounds have not been characterized for potency and efficacy in preclinical studies. The purpose of these experiments was to determine whether some of the more recent synthetic compounds sold as marijuana substitutes have behavioral effects similar to those of Δ-tetrahydrocannabinol (Δ-THC), the pharmacologically active compound in marijuana. The compounds UR-144, XLR-11, AKB-48 (APINACA), PB-22 (QUPIC), 5F-PB-22, and AB-FUBINACA were tested for locomotor depressant effects in male Swiss-Webster mice and subsequently for their ability to substitute for Δ-THC (3 mg/kg, intraperitoneally) in drug discrimination experiments with male Sprague-Dawley rats. UR-144, XLR-11, AKB-48, and AB-FUBINACA each decreased locomotor activity for up to 90 min, whereas PB-22 and 5F-PB-22 produced depressant effects lasting 120-150 min. Each of the compounds fully substituted for the discriminative stimulus effects of Δ-THC. These findings confirm the suggestion that these compounds have marijuana-like psychoactive effects and abuse liability.

Comparable studies

Other preclinical and animal studies on cannabis, most cited first.

Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). hMDR1- and hBCRP-transfected HEK293 cells and hMDR1- and hBCRP-MDCKII cells 2010 In vitro study
Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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