Kevin Richard C, Wood Katie E, Stuart Jordyn, Mitchell Andrew J, Moir Michael, Banister Samuel D, Kassiou Michael, McGregor Iain S
1 School of Psychology, The University of Sydney, NSW, Australia.
2 Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW, Australia.
J Psychopharmacol. 2017 Jun;31(6):757-769. doi: 10.1177/0269881116684336. Epub 2017 Jan 16.
Synthetic cannabinoids (SCs) have rapidly proliferated as recreational drugs, and may present a substantial health risk to vulnerable populations. However, information on possible effects of long-term use is sparse. This study compared acute and residual effects of the popular indazole carboxamide SC compounds AB-PINACA and AB-FUBINACA in adolescent rats with ∆-tetrahydrocannabinol (THC) and control treatments. Albino Wistar rats were injected (i.p.) with AB-PINACA or AB-FUBINACA every second day (beginning post-natal day (PND) 31), first at a low dose (0.2 mg/kg on 6 days) followed by a higher dose (1 mg/kg on a further 6 days). THC-treated rats received equivalent doses of 6 × 1 mg/kg and 6 × 5 mg/kg. During drug treatment, THC, AB-PINACA, and AB-FUBINACA decreased locomotor activity at high and low doses, increased anxiety-like behaviours and audible vocalisations, and reduced weight gain. Two weeks after dosing was completed, all cannabinoid pre-treated rats exhibited object recognition memory deficits. These were notably more severe in rats pre-treated with AB-FUBINACA. However, social interaction was reduced in the THC pre-treated group only. Six weeks post-dosing, plasma levels of cytokines interleukin (IL)-1α and IL-12 were reduced by AB-FUBINACA pre-treatment, while cerebellar endocannabinoids were reduced by THC and AB-PINACA pre-treatment. The acute effects of AB-PINACA and AB-FUBINACA were broadly similar to those of THC, suggesting that acute SC toxicity in humans may be modulated by dose factors, including inadvertent overdose and product contamination. However, some lasting residual effects of these different cannabinoid receptor agonists were subtly different, hinting at recruitment of different mechanisms of neuroadaptation.
合成大麻素（SCs）作为消遣性毒品迅速扩散，可能对弱势群体构成重大健康风险。然而，关于长期使用可能产生的影响的信息却很少。本研究比较了流行的吲唑甲酰胺类合成大麻素化合物AB - PINACA和AB - FUBINACA与∆-四氢大麻酚（THC）及对照处理对青春期大鼠的急性和残留影响。白化Wistar大鼠每隔一天（从出生后第31天开始）腹腔注射AB - PINACA或AB - FUBINACA，开始时为低剂量（6天，每天0.2 mg/kg），随后为高剂量（再6天，每天1 mg/kg）。THC处理组大鼠接受等量的6×1 mg/kg和6×5 mg/kg剂量。在药物治疗期间，THC、AB - PINACA和AB - FUBINACA在高剂量和低剂量时均降低了运动活性，增加了焦虑样行为和可听叫声，并减少了体重增加。给药完成两周后，所有经大麻素预处理的大鼠均表现出物体识别记忆缺陷。这些缺陷在经AB - FUBINACA预处理的大鼠中尤为严重。然而，仅THC预处理组的社交互动减少。给药六周后，AB - FUBINACA预处理降低了细胞因子白细胞介素（IL）-1α和IL - 12的血浆水平，而THC和AB - PINACA预处理降低了小脑内源性大麻素水平。AB - PINACA和AB - FUBINACA的急性影响与THC大致相似，表明人类急性合成大麻素毒性可能受剂量因素调节，包括意外过量和产品污染。然而，这些不同大麻素受体激动剂的一些持久残留影响存在细微差异，这暗示了不同神经适应机制的参与。
