Black Tallan, Barnard Ilne L, Baccetto Sarah L, Greba Quentin, Orvold Spencer N, Austin-Scott Faith V L, Sanfuego Genre B, Onofrychuk Timothy J, Glass Aiden E, Andres Rachel M, Macfarlane Leah M, Adrian Jesse C, Heidt Ashton L, McElroy Dan L, Laprairie Robert B, Howland John G
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada; Department of Anatomy, Physiology, and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
Department of Anatomy, Physiology, and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jan 10;136:111241. doi: 10.1016/j.pnpbp.2024.111241. Epub 2025 Jan 5.
Our understanding of the implications of gestational Cannabis exposure (GCE) remains unclear as Cannabis use increases worldwide. Much of the existing knowledge of the effects of GCE has been gained from preclinical experiments using injections of isolated Δ-tetrahydrocannabinol (THC) at relatively high doses. Few investigations of the effects of GCE to smoke from the whole Cannabis flower have been conducted, despite this being the most common mode of human consumption. Here, we compared the effects of repeated gestational exposure to high-THC or high-cannabidiol (CBD) Cannabis smoke to i.p. THC or i.p. CBD to those of GCE to high-THC or high-CBD Cannabis smoke on litter health and the offspring. We found that injecting phytocannabinoids generally had a more severe impact on measures of maternal and litter health and produced distinct behavioral phenotypes when compared to offspring from dams treated with high-THC and high-CBD smoke during gestation. GCE to high-THC smoke decreased prepulse inhibition (PPI) and MK-801-induced locomotor activity in female adolescent offspring, which normalized in adulthood. GCE to i.p. THC increased exploratory behavior in the open field test in adolescent offspring of both sexes. GCE had a negative impact on offspring performance in the Identical Stimuli Test and Different Stimuli Test with odors regardless of gestational treatment, sex, or age. CBD (i.p) impaired PPI in both male and female offspring in adulthood and increased time spent in proximity during social interaction for male offspring. There were no effects of GCE in the 5 Choice Serial Reaction Time Task. These data establish distinct behavioral phenotypes in the offspring between smoked and injected GCE, further demonstrating that route and specific phytocannabinoid dose produce differential outcomes across offspring lifespan. Smoked Cannabis is still the most common means of consumption, and more preclinical investigation is needed to determine the effects of smoked Cannabis on developmental trajectories.
随着全球大麻使用量的增加，我们对孕期大麻暴露（GCE）影响的理解仍不明确。现有的许多关于GCE影响的知识是通过在临床前实验中以相对高剂量注射分离出的Δ-四氢大麻酚（THC）获得的。尽管吸食整株大麻花是人类最常见的消费方式，但很少有关于GCE对吸食大麻烟雾影响的研究。在这里，我们比较了孕期反复暴露于高THC或高大麻二酚（CBD）大麻烟雾、腹腔注射THC或腹腔注射CBD与孕期暴露于高THC或高CBD大麻烟雾对窝仔健康和后代的影响。我们发现，与孕期接受高THC和高CBD烟雾处理的母鼠所产后代相比，注射植物大麻素通常对母体和窝仔健康指标有更严重的影响，并产生不同的行为表型。孕期暴露于高THC烟雾会降低雌性青春期后代的前脉冲抑制（PPI）和MK-801诱导的运动活动，这些在成年后恢复正常。孕期腹腔注射THC会增加两性青春期后代在旷场试验中的探索行为。无论孕期处理、性别或年龄如何，GCE对后代在相同刺激试验和气味不同刺激试验中的表现都有负面影响。腹腔注射CBD会损害成年雄性和雌性后代的PPI，并增加雄性后代在社交互动中靠近的时间。GCE对5选连续反应时任务没有影响。这些数据确定了吸食和注射GCE后代之间不同的行为表型，进一步证明给药途径和特定植物大麻素剂量在后代整个生命周期中会产生不同的结果。吸食大麻仍然是最常见的消费方式，需要更多的临床前研究来确定吸食大麻对发育轨迹的影响。
