In adolescent rats chronically treated with synthetic cannabinoid WIN55,212-2 (1.2 mg/kg) while exposed to various stressors, offspring appeared more anxiety-prone when stressed themselves. This effect was correlated with increased DNA methylation suggesting epigenetic transfer. Episodic memory appeared unaffected in offspring (Ibn Lahmar Andaloussi et al., 2019). Please note that the dose of WIN55,212-2 would correspond to a very high dose of THC in humans.
The transgenerational effects of adolescent THC exposure on adult offspring was tested in rats. Female Sprague-Dawley rats received Δ(9)-THC (0.1 or 1 mg/kg, i.p.) or vehicle during postnatal days 28-50. As adults, females were mated with drug-naïve males. Potential alterations of the Δ(9)-THC's (0, 0.1, 0.5, and 1 mg/kg, i.p.) and d-amphetamine's (0, 0.1, 0.5, and 1 mg/kg, i.p.) reward-modifying effects were assessed using the curve-shift variant of the intracranial self-stimulation (ICSS) procedure in their adult male F1 offspring. The reward-facilitating effect of the 0.1 mg dose of Δ(9)-THC was abolished in the F1 offspring of females that were exposed to Δ(9)-THC (0.1 or 1 mg/kg), whereas the reward-attenuating effect of the 1 mg dose of Δ(9)-THC remained unaltered. The reward-facilitating effects of 0.5 and 1 mg of d-amphetamine were significantly decreased in the F1 offspring of females that were exposed to Δ(9)-THC (1 mg/kg and 0.1 or 1 mg, respectively). The present results reveal that female Δ(9)-THC exposure during adolescence can diminish the reward-facilitating effects of Δ(9)-THC and d-amphetamine in the adult male offspring. These transgenerational effects occur in the absence of in utero exposure (Pitsilis et al., 2017).
Ibn Lahmar Andaloussi, Z., Taghzouti, K., and Abboussi, O. (2019). Behavioural and epigenetic effects of paternal exposure to cannabinoids during adolescence on offspring vulnerability to stress. Int. J. Dev. Neurosci. Off. J. Int. Soc. Dev. Neurosci. 72, 48–54.
Pitsilis, G., Spyridakos, D., Nomikos, G.G., and Panagis, G. (2017). Adolescent Female cannabinoid Exposure Diminishes the Reward-Facilitating Effects of Δ(9)-Tetrahydrocannabinol and d-Amphetamine in the Adult Male Offspring. Front. Pharmacol. 8, 225.